Brain injuries are complex and can have multiple severe clinical outcomes. Traumatic brain injury (TBI) is the leading cause of central nervous system impairment in these days. More than 1.7 million individuals suffer annually from TBI in the US alone. According to the CDC, the highest incidence of TBI occurs among children 0-4 years old, adolescents 15-19 years old, and adults over 65 years of age. Despite the broad range of the population affected, TBI is still under-served and remains an unexplored pathological condition.
Each year, 35,000 persons in Finland suffer a TBI, 1150 of whom die and 10,000 are left with a permanent impairment. The annual costs of TBI amount to € two billion. The annual figures at the European level are 2.5 million new cases, 75,000 deaths, 400,000 permanent impairments. TBI causes more deaths in the age-group <35 years than all diseases put together, but it affects all age groups. This would imply that worldwide there are over 16.5 million serious TBI's every year.
Traditionally, TBI has been acutely diagnosed and classified by neurological examinations, such as Glasgow Coma Scale (GCS). However, the use of the GCS as a diagnostic tool is subject to a number of important limitations. Recent research has provided evidence that the use of sedative drugs precluded accurate GCS assessment during the first 24 h. Further challenges to diagnosis are presented by the evolving nature of some brain lesions, which can lead to further neurological impairment. In addition, neurological responses after TBI can vary over time for reasons unrelated to the injury. Still further challenges include the trauma subject's possible unconsciousness or inability to communicate.
Neuroimaging techniques, such as x-ray, CT scanning and MRI, are used to provide information on injury magnitude and location, and are not influenced by the aforementioned disadvantages. However, CT scanning has low sensitivity to diffuse brain damage, and availability and utility of MRI is limited. MRI is also very impractical to perform if subjects are physiologically unstable, and can lead to inaccurate diagnoses in military injuries in which metal fragments are common.
Moreover, mild and moderate TBI represent more than 90% of TBI injuries; this injury range represents the greatest challenges to accurate acute diagnosis and outcome prediction. Unlike severe TBI, there is no universally recognized neurologic assessment scale such as the GCS, and many cases of mild TBI are classified as subclinical brain injury (SCI). The widespread recognition of inadequate approaches to diagnose mild TBI suggests the need for significant improvement in the diagnosis and classification of TBI, such as the use of biomarkers to supplement functional and imaging-based assessments. These biomarkers can be altered gene expression, protein or lipid metabolites, or a combination of these changes after traumatic brain injury, reflecting the initial insult (the primary injury) and the evolution of a cascade of secondary damage (the secondary injury). In particular, subclinical brain injury status or SCI could be diagnosed with a biomarker analysis.
As with many injuries, increased serum levels of cytokines and chemokines have been noted post-TBI and, as such, have been proposed as potential surrogate markers for TBI outcome. However, to date, there are no approved biomarkers for the diagnosis or prognosis of TBI. This is because of several obstacles to the development of reliable blood biomarkers of TBI. For instance, the blood-brain barrier (BBB) hinders the assessment of biochemical changes in the brain by use of blood biomarkers in mild TBI, although impaired BBB integrity, as seen in severe TBI, can increase the levels of brain-derived proteins in the blood. Nevertheless, owing to their dilution in the much larger plasma volume, biomarkers that are highly expressed within the central nervous system exist at very low concentrations in blood. Moreover, some potential biomarkers undergo proteolytic degradation in the blood, and their levels might be affected by clearance from blood via the liver or kidney. As a consequence, reliable blood biomarkers have been extremely difficult to identify.
There is thus an identified need for a reliable, simple, and easy-to-use test for brain damage, especially for use in emergency response situations like car accidents and in battlefields.